Figure 3.

The conserved D(E)RY motif in the G protein–binding site. (a) The ionic lock in dark rhodopsin formed by R135^3.50 and E247^6.30. (b) The ionic lock is not present in the crystal structure of carazolol-bound β₂AR. The packing of R^3.50 with L272^6.34 and L275^6.37 is shown with space-filling models of these side chains. (c) Two conformations of the ionic lock region are observed in inverse-agonist bound structures of the β₁AR. Bending near the cytoplasmic end of TM6 results in an electrostatic interaction between R139^3.50 and E285^6.30 ( gray; PDB 2YCX). The alternative straight conformation of TM6 (salmon; PDB 2VT4) moves these two residues apart. (d) Movements of TM6 and TM7 in the β₂AR active state prevent ionic lock formation, and the intrahelical salt bridge between D130^3.49 and R131^3.50 is broken. (e) Packing of β₂AR ( green, with side chains in space-filling representation) and G_sα (orange, shown as a transparent surface). ( f) Interactions of β₂AR with the C-terminal region of bound G_sα. G_sα is shown in orange. Polar interactions are shown with dashed lines. Abbreviations: β₂AR, β₂-adrenergic receptor; G _sα, G_sβ, stimulatory heterotrimeric G protein α and β subunits; PDB, Protein Data Bank; TM, transmembrane.